The calcitonin gene system has been the subject of considerable research in recent years. In particular, studies on rat calcitonin gene expression have demonstrated the generation, by RNA processing, of alternative mRNA species in an apparently tissue specific manner to produce different peptide hormones from a single gene. (Craig R. K. et al (1983) Genetic Engineering 4, 57-125 and Amara et al (1982) Nature 298, 240-244). Each mRNA species encodes a polyprotein cleaved by post translational processing events to yield either rat calcitonin or rat calcitonin gene related peptide (rat CGRP). The rat CGRP is known to be widely distributed in discrete regions of the central and peripheral nervous system where it has been shown to have potent biological activity (Fisher et al (1983) Nature, 305, p 534-536).
In copending European patent applications EP-A1-0070186 and EP-A1-0070675 (R. K. Craig and I. MacIntyre) there are described the production of human calcitonin and a carboxy terminal peptide designated PDN-21 (Katacalcin). Human calcitonin and katacalcin are formed as a polyprotein encoded by the human calcitonin mRNA (Craig et al (1982) Nature, 295, p 345-347).
We have now discovered a region of the human calcitonin gene which is transcribed in human medullary carcinoma cells, and is located distal to the 3' translated region of the human calcitonin mRNA. The region comprises a transcribed intron region, a splice junction, an open reading frame which encodes previously unknown human peptide sequences, and a 3' untranslated region terminating with a tract of poly A residues. One of the peptides is apparently an analogue of rat CGRP, which analogue we refer to hereinafter as human calcitonin gene related peptide (human CGRP).